ReviewMovement disorders : official journal of the Movement Disorder Society2023
The Endotoxin Hypothesis of Parkinson's Disease.
Review in Movement disorders : official journal of the Movement Disorder Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Omics research in Parkinson's disease: evolution, integrated analysis, pathogenic mechanisms, biomarkers, and therapeutic targets.Frontiers in molecular neuroscience · 2026Pooled it
- Review
- Gut microbiome dysbiosis, short-chain fatty acid depletion and implications for neuroinflammation in atypical parkinsonian syndromes - a systematic review of patient cohorts.Journal of Parkinson's disease · 2026Review
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Gut-brain axis dysregulation in Parkinson's disease: Mechanisms linking microbiota to neuroinflammation and α-synuclein pathology.Journal of pharmaceutical analysis · 2026Review
- β-Amyloid (Aβ) and Human Cathelicidin LL-37: Two Sides of the Same Coin?International journal of molecular sciences · 2026Review
- Exploring Mechanistic Targets ofInternational journal of molecular sciences · 2026Article
- Regulator of G protein signaling 10: a critical regulator of chronic systemic inflammation in parkinson's disease.Journal of neuroinflammation · 2026Review
- The Influence of Gut Microbiome on Alpha-Synuclein Aggregation: Implications for Parkinson's Disease Pathogenesis.Molecular neurobiology · 2026Review
- Gut-Brain Signaling in Parkinson's Disease: A Narrative Review.International journal of molecular sciences · 2026Review
- A 3D gut-brain-vascular platform for bidirectional crosstalk in gut-neuropathogenesis.Nature communications · 2026Article
- Endotoxins and Metabolic Endotoxemia in Obesity and Associated Noncommunicable Diseases: A Focus on Sex Differences.Biomolecules · 2026Review
- Microglial low-affinity FcγR mediates the phagocytic elimination of dopaminergic neurons in Parkinson's disease degeneration.NPJ Parkinson's disease · 2026Article
- From dysbiosis to dysfunction: specific gut microbes and metabolites in the pathogenesis of Parkinson's disease.Sustainable microbiology · 2026Review
- Modulation of Behavioral, Biochemical, Immunomodulatory, and Transcriptional Profiles by the StrainInternational journal of molecular sciences · 2025Article
- Psychobiotics at the Frontiers of Neurodegenerative and Neuropsychiatric Research.Microorganisms · 2025Review
- White Blood Cells in Neurodegenerative Diseases in the Context of Neuroinflammation.Molecular neurobiology · 2025Review
- Altered gut microbial functional pathways in people with irritable bowel syndrome enable precision health insights.BMC gastroenterology · 2025Article
- Polyphenols Bioactive Metabolites, and Their Anti-Biofilm and Neuroprotective Potential.Foods (Basel, Switzerland) · 2025Review
- Metabolic reprogramming in ischemic stroke: when glycolytic overdrive meets lipid storm.Cell death & disease · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to the pathogenesis of this disorder. LPS endotoxins are found in, and released from, the outer membrane of Gram-negative bacteria, for example in the gut. It is proposed that gut dysfunction in early PD leads to elevated LPS levels in the gut wall and blood, which promotes both α-synuclein aggregation in the enteric neurons and a peripheral inflammatory response. Communication to the brain via circulating LPS and cytokines in the blood and/or the gut-brain axis leads to neuroinflammation and spreading of α-synuclein pathology, exacerbating neurodegeneration in brainstem nuclei and loss of dopaminergic neurons in the substantia nigra, and manifesting in the clinical symptoms of PD. The evidence supporting this hypothesis includes: (1) gut dysfunction, permeability, and bacterial changes occur early in PD, (2) serum levels of LPS are increased in a proportion of PD patients, (3) LPS induces α-synuclein expression, aggregation, and neurotoxicity, (4) LPS causes activation of peripheral monocytes leading to inflammatory cytokine production, and (5) blood LPS causes brain inflammation and specific loss of midbrain dopaminergic neurons, mediated by microglia. If the hypothesis is correct, then treatment options might include: (1) changing the gut microbiome, (2) reducing gut permeability, (3) reducing circulating LPS levels, or (4) blocking the response of immune cells and microglia to LPS. However, the hypothesis has a number of limitations and requires further testing, in particular whether reducing LPS levels can reduce PD incidence, progression, or severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.